A new therapeutic avenue for bronchiectasis: Dry powder inhaler of ciprofloxacin nanoplex exhibits superior ex vivo mucus permeability and antibacterial efficacy to its native ciprofloxacin counterpart

Publication date: 25 August 2018Source: International Journal of Pharmaceutics, Volume 547, Issues 1–2Author(s): The-Thien Tran, Celine Vidaillac, Hong Yu, Valerie F.L. Yong, Dan Roizman, Ravishankar Chandrasekaran, Albert Y.H. Lim, Teck Boon Low, Gan Liang Tan, John A. Abisheganaden, Mariko Siyue Koh, Jeanette Teo, Sanjay H. Chotirmall, Kunn HadinotoAbstractNon-cystic fibrosis bronchiectasis (NCFB) characterized by permanent bronchial dilatation and recurrent infections has been clinically managed by long-term intermittent inhaled antibiotic therapy among other treatments. Herein we investigated dry powder inhaler (DPI) formulation of ciprofloxacin (CIP) nanoplex with mannitol/lactose as the excipient for NCFB therapy. The DPI of CIP nanoplex was evaluated against DPI of native CIP in terms of their (1) dissolution characteristics in artificial sputum medium, (2) ex vivo mucus permeability in sputum from NCFB and healthy individuals, (3) antibacterial efficacy in the presence of sputum against clinical Pseudomonas aeruginosa strains (planktonic and biofilm), and (4) cytotoxicity towards human lung epithelial cells. Despite their similarly fast dissolution rates in sputum, the DPI of CIP nanoplex exhibited superior mucus permeability to the native CIP (5–7 times higher) attributed to its built-in ability to generate highly supersaturated CIP concentration in the sputum. The superior mucus permeability led to the CIP nanoplex’s higher antibacterial efficacy (>3 log10 CFU...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research